WO2013087665A2

WO2013087665A2 - Cosmetic composition for skin or hair care

Info

Publication number: WO2013087665A2
Application number: PCT/EP2012/075164
Authority: WO
Inventors: Geneviève BONNECHÈRE - DELSTANCHE; Olivier Henry
Original assignee: Dequest Ag
Priority date: 2011-12-12
Filing date: 2012-12-12
Publication date: 2013-06-20
Also published as: EP2790654A2; WO2013087665A3

Abstract

The present invention relates to the use of a composition comprising, in a cosmetically acceptable medium, a carboxylated fructan compound for the cosmetic treatment of skin, hair or keratin substances. The present invention also relates to a composition comprising carboxylated fructan compound for use as medicine, in particular for the therapeutic or prophylaxis treatment of dermatologic and allergic diseases or disorders.

Description

COSMETIC COMPOSITION FOR SKIN OR HAIR CARE

TECHNICAL FIELD

[0001 ] The present invention relates to a composition comprising a carboxylated fructan compound, such as carboxymethylinulin for skin or hair care.

DESCRIPTION OF RELATED ART

[0002] Women and men tend to want to look young now as long as possible and consequently seek to blur the signs of skin ageing, such as loss of firmness, elasticity, tone and/or flexibility of the skin and the formation of wrinkles and fine lines. In this respect, advertising and fashion show of products for as long as possible to keep skin radiant and wrinkle-free, brand of young skin, especially as the physical acts on the psyche and/or on morale.

[0003] Human skin consists of two compartments, namely a superficial compartment, the epidermis, and a deep compartment, the dermis. The epidermis is in contact with the outside environment. Its role is to protect the body from dehydration and external aggressions, whether chemical, mechanical, physical or infectious.

[0004] The main clinical signs of ageing skin include the appearance of fine lines and/or wrinkles, increasing with age. These wrinkles are deep, medium or superficial, affecting especially the nasolabial folds, periorbital area, the contour of the lips, forehead (frown lines), those fine lines and wrinkles resulting in a depression or grooves the surface of the skin.

[0005] Various methods have been proposed to fight against wrinkles and fine lines, for which the use of products containing skin care cosmetic active agent is necessary (anti-wrinkle, moisturizing, firming in particular). To this end, hyaluronic acid may be used in many cosmetic applications, such as anti-ageing applications. It also plays an important role in hydration and skin elasticity. The hyaluronic acid used in cosmetic formulations is generally in the form of sodium hyaluronate. To increase its effectiveness, it has also been proposed for use in injection, mesotherapy or as filler for wrinkles. EP191 1439 discloses solid compositions comprising hyaluronic acid applicable to human skin and gellable on contact with water. The compositions are prepared in the form of a flexible solid film that can be used in cosmetic or therapeutic applications. EP 2347755 discloses a cosmetic composition comprising hyaluronic acid to reduce wrinkles and/or depth pores. [0006] However, hyaluronic acid and salts thereof have major drawbacks. Such derivatives are prepared by enzymatic or biosynthesis by Streptococcus and have a solubility in water lower than 1wt.% at room temperature. Hence, aqueous solutions comprising hyaluronic acid derivatives tend to form gels or form viscous solutions which are hardly processable.

[0007] The present invention addresses the problem of the state of the art and at least partly overcome the above-discussed drawbacks of the prior art.

SUMMARY OF THE INVENTION

[0008] The present invention relates to a carboxylated fructan compound for cosmetic or therapeutic use. In a first aspect, the present invention refers to a carboxylated fructan compound or a pharmaceutical composition comprising a carboxylated fructan compound for use as medicine. Such therapeutic effect may be obtained due to the influence of the carboxylated fructan compound on the filaggrin content in epidermis. In another aspect, the present invention relates to the cosmetic use of a carboxylated fructan compound for the cosmetic treatment of skin, hair or keratin substances. The carboxylated fructan compound may be included in a cosmetic composition further comprising a cosmetically acceptable medium. The performance of the carboxylated fructan compound can be further enhanced when used in combination with at least one salt of mono or diglycolate. The presence of at least one salt of mono or diglycolate in the composition allows favoring the hydration of the epidermis. The hydration of the epidermis is important to correct depression of the skin or to remove ageing effect on the skin. The carboxylated fructan compound alone or in combination with said at least one salt of mono or diglycolate is suitable as hyaluronic acid substituent. Indeed, the carboxylated fructan compound alone or in combination with said at least one salt of mono or diglycolate exhibits similar or better results than hyaluronic acid regarding cosmetic treatments. Unexpected therapeutic effect of the carboxylated fructan compound alone or in combination with said at least one salt of mono or diglycolate was also observed.

[0009] In another aspect, the present invention relates to a method for hardening or hydrating the epidermis, or enhancing barrier properties of the epidermis, or increasing the content of filaggrin of the epidermis comprising the step of applying a present composition comprising the carboxylated fructan compound optionally in combination with said at least one salt of mono or diglycolate, onto the surface of the epidermis. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Fig. 1 represents the percentage of moisture absorption of various samples at 81 % of relative humidity over time.

[001 1 ] Fig. 2 represents the percentage of moisture absorption of various samples at 43% of relative humidity over time.

[0012] Fig. 3 represents the percentage of moisture retention of various samples at 43% of relative humidity over time.

[0013] Fig. 4 represents the percentage of moisture retention of various samples in presence of silica gel over time.

[0014] Fig. 5 represents the electrical resistance (Ohm/10^{3 *} cm²) of the epidermis when various samples are applied thereon.

[0015] Fig. 6 represents the relative filaggrin content of various samples comprising either carboxymethylinulin or hyaluronic acid.

DETAILED DESCRIPTION OF THE INVENTION

[0016] The present invention relates to a carboxylated fructan compound. Said carboxylated fructan compound may be selected from the group consisting of:

(a) carboxyalkylfructan having from 1 to 4 carbon atoms in the alkyl moiety,

(b) dicarboxyfructan having a degree of oxidation (DO) of from 10 to 100% expressed as a molar percentage of monosaccharide units converted into the corresponding dicarboxy analogues,

(c) 6-carboxyfructan,

(d) fructan polycarboxylic acid, having a degree of carboxyalkylation or carboxyacylation of from 0.2 to 3.0, or

(e) mixtures thereof.

[0017] Fructans used as starting material for producing the carboxylated fructans are oligo- and polysaccharides which have a majority of anhydrofructose units, and can have a polydisperse chain length distribution and can be of straight- or branched-chain. Preferably the fructan contains mainly beta-2,1 bonds, as in inulin. The fructans, and the preferred inulin, can be products obtained directly from a vegetable source or other sources as well as products in which the average chain length has been modified, increased or reduced, by fractionation, enzymatic synthesis or hydrolysis.

[0018] Carboxylated fructans with modified average chain length can be made from fructans with enzymatically increased chain length, fructan hydrolysis products having shortened chains and fractionated products having a modified chain length. Fractionating of fructans such as inulin can be achieved, for example, by means of known techniques including low temperature crystallization (see WO 94/01849), column chromatography (see WO 94/12541 ), membrane filtration (see EP-A-0440074, EP-A-0627490) or selective precipitation with alcohol. Hydrolysis to yield shorter fructans can be carried out, for example, enzymatically (endo-insulase), chemically (water and acid) or by heterogeneous catalysis (acid column). Reduced, oxidized, hydroxyalkylated and/or crosslinked fructans can also represent suitable starting materials to produce the carboxylated fructans. The fructans have an average chain length (degree of polymerization, DP) of at least 3 to about 1000. Preferably, the average chain length is from 3 to 60, in particular of from 5 to 30 monosaccharide units. A preferred fructan is inulin (beta-2,1 -fructan) or a modified inulin, and these preferred carboxylated inulins and modified inulins are made accordingly.

[0019] Dicarboxyfructans can be obtained through oxidation of the fructan raw material, and accordingly the preferred dicarboxyinulins can be obtained through oxidation of the inulin raw material. The anhydrofructose units are converted, with ring opening, into dicarboxy(hydroxyethoxy)ethyleneoxy units. The oxidation can proceed in one step with hypohalite, as described in WO 91/17189, or in two steps with periodate and chlorite, as described in WO 95/12619. Preferred degrees of oxidation (DO) are in the range of from 20 to 90%, the DO being the (molar) percentage of monosaccharide units converted into the corresponding dicarboxy analogues.

[0020] Fructan polycarboxylic acid is preferably inulin polycarboxylic acid which can be prepared by successive oxidation and carboxyalkylation of the selected starting material. The material has a DO (degree of oxidation) of from 0.2 to 2.0 and a degree of carboxy-alkyl/-acyl substitution of from 0.2 to 3, preferably from 1.5 to 2.7.

[0021] 6-carboxyfructan is preferably 6-carboxy inulin, which is a well known material. It can be obtained by oxidation in accordance with the method of WO 95/07303.

[0022] In preferred embodiment, the carboxylated fructan compound may be selected from the group consisting of carboxyalkylinulin having 1 or 2 carbon atoms in the alkyl moiety (e.g. carboxymethylinulin and/or carboxyethylinulin) and having a degree of substitution of from 1 .5 to 2.7. Carboxymethylinulin can be prepared by reaction of the fructan with chloroacetic acid as described in WO 95/15984. Carboxylethylinulin can be prepared in accordance with the method of WO 96/34017.

[0023] In a preferred embodiment, the carboxylated fructan compound may be carboxymethylinulin having a degree of substitution of from 1 .5 to 2.7. Most preferably, the carboxylated fructan compound may be carboxymethylinulin having a degree of substitution of 2.0 or 2.5. Compositions comprising carboxymethylinulin having a degree of substitution of 2.0 or 2.5 exhibit better performance with respect to the moisture absorption, the hydration of the epidermis, or the enhancement of the barrier properties of the epidermis. Excellent results were also obtained with respect to the in- vitro experiment, in particular to favor the increase of the content of filaggrin of the epidermis.

[0024] The carboxylated fructan compound may be combined with at least one salt of mono or diglycolate to form a composition. Preferably, said composition may comprise from 1 to 50 wt.% of at least one salt of mono- or di-glycolate, preferably from 1 to 20 wt.%, more preferably from 1 to 10 wt.%, with respect to the total weight of the composition. The terms "mono glycolate" or "glycolate" both refer to a salt of glycolic acid HO-C(0)-CH₂OH. The term "diglycolate" refers to a salt of diglycolic acid 0(CH₂COOH)₂.

[0025] In particular, said composition may comprise a mixture of glycolate and diglycolate salts. The content of glycolate salt may range from 0.5 to 10 wt% with respect to the total weight of the composition. The content of diglycolate salt may range from 0.5 to 10 wt% with respect to the total weight of the composition. In particular, the composition may comprise from 1 to 20 wt% of a mixture of mono and diglycolate salts, preferably from 1 to 10 wt% with respect to the total weight of the composition. Said salt may be alkaline metal salt or alkaline earth metal salt. For example, the salt may be lithium, sodium, potassium, magnesium, or calcium salt. Even if excellent results were obtained with the composition comprising only the carboxylated fructan compound, better performance was surprisingly achieved when the composition further comprise at least one salt of mono or diglycolate salt. Indeed, the presence of said mono or diglycolate salt in the present composition improves the hydration and/or the barrier properties of the epidermis. In presence of said at least one salt of mono or diglycolate salt the content of filaggrin of the epidermis can be increased which favors the improvement of the skin appearance. Hence, wrinkles, scarring and others depressions in the skin can be corrected by the present composition, and preferably when said composition further comprises at least one salt of mono or diglycolate salt. The present composition may also lower skin and/or mucosa ageing.

[0026] The present composition, with or without said at least one salt of mono or diglycolate salt, may be added to cosmetic composition or formulation used to protect skin and to prevent dehydration of the skin, for example sunscreen composition. Alternatively, the present composition may be suitable as protective agent for hair or skin in a cosmetic composition or formulation. The present composition may be also suitable as skin or hair protective agent in hand and/or body and/or hair care composition. The positive effect of the present composition on the skin, in particular on the hydration of the skin is exemplified hereunder.

[0027] In a particular embodiment, a composition consisting of a carboxylated fructan compound as defined above and from 1 to 50 wt.% of at least one salt of mono- or di-glycolate, preferably from 1 to 20 wt.%, more preferably from 1 to 10 wt.%, with respect to the total weight of the composition, is provided.

[0028] The present invention relates to the use, in a cosmetically acceptable medium, of the composition as defined above for the cosmetic treatment of skin, hair or keratin substances. A cosmetic composition is therefore prepared. Said cosmetic composition further comprises the well-known ingredient or additives needed to prepare a cosmetic composition. Hence, the present invention provides a cosmetic composition comprising a carboxylated fructan compound as defined above. The cosmetic composition further comprises from 1 to 100 wt% of at least one salt of mono- or di-glycolate, preferably from 1 to 25 wt%, more preferably from 1 to 12 wt%, calculated on the basis of the carboxylated fructan compound. In particular, said at least one salt of mono- or di-glycolate may be a mixture of glycolate and diglycolate salts. The content of glycolate salt may range from 0.5 to 25 wt% calculated on the basis of the carboxylated fructan compound. The content of diglycolate salt may range from 0.5 to 25 wt% calculated on the basis of the carboxylated fructan compound.

[0029] Preferably, the content of said carboxylated fructan compound in the cosmetic composition may range from 0.0005 wt% to 10wt% based on the total weight of the cosmetic composition, preferably from 0.001 wt% to 5 wt% based on the total weight of the cosmetic composition, more preferably, from 0.005 wt% to 5 wt% based on the total weight of the cosmetic composition.

[0030] The present composition comprising carboxylated fructan compound, as defined above, alone or in combination with said at least one salt of mono or diglycolate salt may be suitable to correct wrinkles, scarring and others depressions in the skin, or for lowering skin and/or mucosa ageing. Furthermore, the carboxylated fructan compound, as defined above, alone or in combination with said at least one salt of mono or diglycolate salt may be used as skin or hair protective agent in a cosmetic composition, hand and/or body and/or hair care composition, sunscreen composition, or hand dishwashing detergent composition. The present composition is also suitable for anti-ageing cosmetic use.

[0031] In another aspect of the present invention, a method for hardening or hydrating the epidermis, or enhancing barrier properties of the epidermis, or increasing the content of filaggrin of the epidermis is provided. Said method comprises the step of applying the carboxylated fructan compound, as defined above, alone or in combination with said at least one salt of mono or diglycolate salt onto the surface of the epidermis, preferably whereon the firmness of said surface of the epidermis is reduced. This lack of firmness may be due, for example, to the dehydration of the epidermis or a lower content of filaggrin.

[0032] Alternatively, the carboxylated fructan compound, as defined above, alone or in combination with said at least one salt of mono or diglycolate salt may be injected within the epidermis. This kind of injection is well-known in the cosmetic field. For example, the composition may be injected in the wrinkles.

[0033] The present composition may be suitable as moisture retention or absorption agent, or as epidermis hydrating agent or humectants.

[0034] Alternatively, the present composition may be used as textile protective agent in laundry detergents, or fabric softeners.

[0035] In another aspect, the present invention provides a carboxylated fructan compound, as defined above, or a composition according to the present invention for use as medicine. The present composition may comprise a carboxylated fructan compound, as defined above, and optionally at least one salt of mono- or diglycolate as defined above.

[0036] In a preferred embodiment, the carboxylated fructan compound as well as the composition according to the present invention may be used for the treatment or prophylaxis of dermatologic or allergic diseases or disorders. Said dermatologic or allergic diseases or disorders are selected from the group consisting of contact allergy, psoriasis, plaque psoriasis, psoriasis vulgaris, localized pustular psoriasis, pustule psoriasis, Hallopeau localized continuous achrodermatitis, pustular palm psoriasis, pustular sole psoriasis, generalized pustular psoriasis, von Zumbuch generalized pustular psoriasis, milia psoriasis, Hallopeau generalized continuous dermatitis, herpetiform impetigodermatitis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, numular dermatitis, generalized exfoliative dermatitis, statis dermatitis, perioral dermatitis, acne, rosacea, boils, carbuncles, pemphigus, cellulitis, Graver's disease, hidradenitis suppurativa, lichen planus, chronic lichen simplex, rhinophyma, pseudofolliculitis barbae, inflammatory reactions, drug eruptions, erythema, erythema multiforme, erythema nodosum, granuloma annulare, eczema, xerosis, ichthyosis, epidermolytic hyperkeratosis, keratoses, pruritis, cradle cap, scales, fresh stretch marks, dermatoses, burns, skin hypersensitivity reactions (including poison ivy and poison oak), decubitus ulcers, pressure ulcers, diabetic ulcers, epidermolysis bullosa, eczematoid dermatitis, pemphigus, bullous pemphigoid, epidermolysis bullosa, urticaria, angioedema, vasculitides, dermal eosinophilia, vitiligo, alopecia areata, skin cancers, cutaneous T cell lymphoma, basal cell carcinoma, nodular basal cell carcinoma, cystic basal cell carcinoma, cicatricial basal cell carcinoma, infiltrative basal cell carcinoma, Micronodular basal cell carcinoma, superficial basal cell carcinoma, pigmented basal cell carcinoma, Jacobi ulcer, fibroepithelioma of Pinkus, polypoid basal cell carcinoma, pore-like basal cell carcinoma, aberrant basal cell carcinoma, squamous cell carcinoma, adenoid squamous cell carcinoma, clear cell squamous cell carcinoma, spindle cell squamous cell carcinoma, signet-ring cell squamous cell carcinoma, basaloid squamous cell carcinoma, verrucous carcinoma, keratoacanthoma, Bowen's disease, Marjolin's ulcer, melanoma, lentigo maligna, lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, mucosal melanoma, nodular melanoma, polypoid melanoma, desmoplastic melanoma, amelanotic melanoma, soft-tissue melanoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi's sarcoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, Pagets's disease, atypical fibroxanthoma, leimyosarcoma, angiosarcoma, Merkel cell carcinoma, allergic rhinitis, hay fever and food allergy.

[0037] The composition or the carboxylated fructan compound according to the present invention may be used for the treatment or prophylaxis of diseases or disorders associated with filaggrin deficiencies in the epidermis.

[0038] Preferably, said dermatologic or allergic diseases or disorders may be selected from the group consisting of psoriasis, plaque psoriasis, psoriasis vulgaris, localized pustular psoriasis, pustule psoriasis, Hallopeau localized continuous achrodermatitis, pustular palm psoriasis, pustular sole psoriasis, generalized pustular psoriasis, von Zumbuch generalized pustular psoriasis, milia psoriasis, Hallopeau generalized continuous dermatitis, herpetiform impetigodermatitis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, numular dermatitis, generalized exfoliative dermatitis, statis dermatitis, perioral dermatitis, eczema, xerosis, ichthyosis, epidermolytic hyperkeratosis, keratoses, pruritis, eczematoid dermatitis, allergic rhinitis, contact allergy, hay fever and food allergy.

[0039] The present invention further provides a pharmaceutical preparation comprising the carboxylated fructan compound according to the present invention. Said pharmaceutical preparation may comprise a therapeutically effective amount of the carboxylated fructan compound according to the present invention in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. The pharmaceutical preparation further comprises from 1 to 100 wt% of at least one salt of mono- or di- glycolate, preferably from 1 to 25 wt%, more preferably from 1 to 12 wt%, calculated on the basis of the carboxylated fructan compound. In particular, said at least one salt of mono- or di-glycolate may be a mixture of glycolate and diglycolate salts. The content of glycolate salt may range from 0.5 to 25 wt% calculated on the basis of the carboxylated fructan compound. The content of diglycolate salt may range from 0.5 to 25 wt% calculated on the basis of the carboxylated fructan compound. The carboxylated fructan compound and said at least one salt of mono- or di-glycolate may be in the form of a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co- crystal thereof. Preferably, the content of said carboxylated fructan compound in the pharmaceutical preparation may range from 0.0005 wt% to 10wt% based on the total weight of the pharmaceutical preparation, preferably from 0.001 wt% to 5 wt% based on the total weight of the pharmaceutical preparation, more preferably, from 0.005 wt% to 5 wt% based on the total weight of the pharmaceutical preparation.

[0040] Said pharmaceutical preparation may be used for the treatment or prophylaxis of dermatologic or allergic diseases or disorders, or for the treatment or prophylaxis of diseases or disorders associated with filaggrin deficiencies in the epidermis as defined above.

[0041] In a further aspect of the present invention, a composition comprising a carboxylated fructan compound as defined above, and 1 to 100 wt.% of at least one salt of mono- or diglycolate, preferably from 1 to 25 wt.%, more preferably from 1 to 12 wt.%, calculated on the basis of the carboxylated fructan compound, is provided. Preferably, the carboxylated fructan compound is selected from carboxyalkylinulin having 1 or 2 carbon atoms in the alkyl moiety (e.g. carboxymethylinulin and/or carboxyethylinulin) and having a degree of substitution of from 1 .5 to 2.7. Most preferably, the carboxylated fructan compound may be carboxymethylinulin having a degree of substitution of from 1 .5 to 2.7. In particular, the carboxylated fructan compound may be carboxymethylinulin having a degree of substitution of 2.0 or 2.5. Preferably, said at least one salt of mono- or diglycolate may be a mixture of mono and diglycolate salts. The content of glycolate salt may range from 0.5 to 25 wt% calculated on the basis of the carboxylated fructan compound. The content of diglycolate salt may range from 0.5 to 25 wt% calculated on the basis of the carboxylated fructan compound. Said salt may be alkaline metal salt or alkaline earth metal salt. For example, the salt may be lithium, sodium, potassium, magnesium, or calcium salt. The composition may be a powder or an aqueous solution.

Examples

[0042] Example 1 : Preliminary absorption and retention tests

[0043] The absorption and retention abilities of the compositions according to the present invention were evaluated and compared to hyaluronic acid-containing compositions. The moisture absorption tests were carried out at 81 % and 43% relative humidity. Prior to the tests, the samples were dried over P₂0₅ in vacuo for 24h. In the moisture absorption test, dry samples, each 0.5g, were putted into a saturated (NH₄)₂S0₄ dessicator (81 % relative humidity, RH), a saturated Na₂C0₃ dessicator (43% RH). The weight gain of the samples was recorded at pre- set time intervals over at least 90h and calculated as the percentage of moisture absorption (Ra). Ra (%)= (Wn - W0)/ W0 X 100 wherein W0 and Wn are the weights of samples before and after putted into the dessicators. Seven compositions, in powder form, were compared. Composition A comprises carboxymethylinulin (degree of substitution was 2.0) and 6.5wt% of a mixture of sodium glycolate and sodium diglycolate. Composition D comprises carboxymethylinulin (degree of substitution was 2.5) and 9wt% of a mixture of sodium glycolate and sodium diglycolate. Composition B comprises carboxymethylinulin (degree of substitution was 2.5) without mono or diglycolate salts. Composition C comprises pure carboxymethylinulin (degree of substitution was 2.5). Compositions A-D were also compared to compositions comprising either inulin, hyaluronic acid (HA) or xilogel®. Xilogel® is a polysaccharide known to be an alternative to hyaluronic acid. Results were summarized in table 1 below and Fig. 1. Fig. 1 represents the percentage of moisture absorption (Ra %) versus the time expressed in hours.

Table 1

4h 20h 24h 28h 44h 48h 52h 69h 73h 77h 94h

Comp. A 18 68 74 87 1 14 137 148 148 148 148 148

Comp. B 4 16 16 16 23 24 25 26 27 28 28

Comp. C 5 14 14 14 17 17 17 22 23 24 25

Comp. D 18 47 58 64 80 85 88 109 1 13 121 138 HA 26 29 58 59 61 61 62 65 65 64 63

Xilogel® 18 22 22 22 22 22 22 23 23 24 25

Inulin 10 13 26 26 28 30 30 30 30 30 30

Compositions A and D, which comprise carboxymethylinulin and a mixture of sodium glycolate and sodium diglycolate, show better performance than the composition comprising hyaluronic acid. Indeed, the weight gain was around 50% for hyaluronic acid while the weight gain was greater than 140% after 94 hours for compositions A and D according to the present invention. This result was totally unexpected at the time of the invention. Compositions B and C were slightly less efficient than hyaluronic acid but absorption properties were observed with a weight gain around 20% which was comparable to inulin or xilogel.

[0044] The experiment was reproduced under a relative humidity of 43%. The results were listed in table 2 and represented in Fig. 2.

Table 2

[0045] The results obtained at 43% of relative humidity had the same profile than the results obtained at 81 % of relative humidity. Compositions A and D exhibited excellent absorption properties. Indeed, a weight gain of 190% and 143% was obtained for compositions A and D after 94 hours respectively, while 81 % was obtained with hyaluronic acid. Compositions B and C achieved a weight gain of 73% and 37% after 94 hours respectively which was acceptable results.

[0046] With regard to the moisture retention test, wet samples were firstly prepared by adding 10% water to each sample and then were putted into a dessicator with 43% of relative humidity and silica gel. The moisture retention ability was evaluated by the percentage of residual water of wet sample (Rh). Rh(%)= Hn/ HO X 100 wherein HO and Hn are the weights of water in sample before and after putted in the dessicators. The results obtained with 43% of relative humidity were listed in table 3 and represented in Fig. 3 wherein the percentage of moisture retention was in function of time expressed in hours.

Table 3

[0047] The moisture retention ability of the compositions A and D was similar to the moisture retention ability of hyaluronic acid. After 94 hours, the moisture retention was 50%, 57% and 45% for composition A, D and hyaluronic acid respectively. Compositions B and C reached lower values comparable to values obtained with xilogel®.

[0048] The retention moisture experiment was reproduced under ambient humidity but in presence of silica gel. The results obtained were listed in table 4 and represented in Fig. 4 wherein the percentage of moisture retention was in function of time expressed in hours.

Table 4

[0049] Results obtained with compositions B and C were similar to those obtained with xilogel®. The same performance profile was observed. Composition A and the composition comprising hyaluronic acid show significant weight loss, e.g. 18% and 15% after 94 hours. The results obtained with composition D were acceptable since a weight loss of 55% was obtained.

[0050] The moisture retention testing shows that the compositions A and D according to a preferred embodiment of the present invention are efficient compositions for moisture retention and have at least comparable performance with respect to the hyaluronic acid performance. Results obtained in silica gel show that compositions A and D are able to release part of the water absorbed. Compositions B and C without glycolate salts show acceptable absorption performances comparable to xilogel®. In addition, the retention ability of such compositions was enhanced overtime compared to hyaluronic acid. Example 1 shows that a composition comprising a carboxylated fructan compound has the ability to control the moisture absorption or retention. This effect is enhanced when the composition further comprise at least one salt of mono or di-glycolate. The ability of the mono or diglycolate to further improve the retention/adsorption properties of the composition was unexpected.

[0051] Example 2: In vitro testing

[0052] Further the preliminary testing disclosed above, compositions according to the present invention were considered as potential candidates for cosmetic applications. In vitro testing was performed to demonstrate the effect of compositions according to the present invention on the epidermis. Hence, cytotoxicity and influence of the composition according to the present invention on epidermis were evaluated.

[0053] Cytotoxicity of five samples was tested. The first sample is a control sample, two samples contain hyaluronic acid at 10μg ml and 50μg ml respectively, and two other samples contain the composition A described above having a carboxymethylinulin content of 10μg ml and 50μg ml respectively. As mentioned above, the composition A further comprises a mixture of sodium glycolate and sodium diglycolate. The overall content of said sodium glycolate and sodium diglycolate was approx. 6.5wt% with respect to the total weight of carboxymethylinulin in the sample. In particular, composition A comprises 3.5wt% of sodium glycolate and 3wt% of sodium diglycolate with respect to the total weight of carboxymethylinulin in the composition. For each sample, the morphology of epidermis was compared by colored histological view. At such concentrations, the epidermis was not altered by compositions of the present invention. Another experiment shows that alteration of the epidermis was only observed for compositions according to the present invention having a carboxymethylinulin content of 250 μg ml.

[0054] Barrier properties of the epidermis was evaluated following the procedure disclosed in Gu et al., Exp. Dermatol., 19, e336-e339, 2010. Measuring the electrical resistance of the epidermis in presence of a composition comprising carboxymethylinulin and a mixture of glycolate and diglycolate salts, or comprising hyaluronic acid allows the evaluation of the barrier properties of the epidermis. The control sample is a sample of non-treated epidermis. Fig. 5 represents the electrical resistance of the epidermis when the composition A having a carboxymethylinulin content of 10 μg ml or 50μg ml was applied thereon. The measurement was performed after 14 days of treatment. The greater was the electrical resistance; the lower was the permeability of the epidermis. Hence, when an increase of the epidermis electrical resistance was observed, it means that the impermeability of the epidermis was reinforced and that the tissue was not altered which is essential for cosmetic applications. The measurement performed when the composition A was applied on the epidermis showed an increase in electrical resistance up to 130% compared to the control sample at 10μg ml. The value obtained with a sample at a concentration of 50μg ml was 1 1 1 %. It was unexpected to obtain such results which demonstrate that the present composition is an alternative to hyaluronic acid for cosmetic applications. Indeed, the epidermis electrical resistance was 102% and 137% at 10μg ml and 50μg ml respectively in presence of hyaluronic acid. Hence, the present composition provides the same results than hyaluronic acid at lower concentration which was unexpected. The composition according to the present invention comprising a carboxylated fructan compound, such as carboxymethylinulin, and preferably further comprising at least one salt of mono or diglycolate, is able to enhance barrier properties of the epidermis. Hence, the epidermis exhibits a low permeability and a cohesive structure.

[0055] The amount of filaggrin in presence of the composition A or HA was also evaluated. Filaggrin is a hydration marker of the epidermis. The proteolysis of filaggrin generates hygroscopic molecules acting as a sponge and which allows increasing the water content of the epidermis. Higher content in filaggrin will favor the correction of wrinkles or skin depression. Fig. 6 represents the relative filaggrin content in epidermis evaluated for five samples: a control sample (non-treated epidermis), in presence of the composition A as described above (carboxymethylinulin concentration of 10μg ml or 50μg ml) or in presence of hyaluronic acid at 10μg ml or 50μg ml. The values were relative values expressed compared to the effective amount of filaggrin obtained with the non treated sample. The amount of filaggrin was defined at a value of 100 with the non treated sample. The filaggrin content was 133 and 190 for composition A having a carboxymethylinulin content of 10Mg/ml and δθμς/ηηΐ respectively. The filaggrin content obtained for samples comprising hyaluronic acid was 104 and 195 respectively. The filaggrin content was higher in presence of the composition A, having a carboxymethylinulin content of 1 C^g/ml, than in presence of a composition comprising 1 C^g/ml of hyaluronic acid. Hence, the present composition can be used in cosmetic applications instead of hyaluronic acid. At higher concentration of carboxymethylinulin, the filaggrin content obtained with the composition A was comparable to the one of hyaluronic acid. Controlling the amount of filaggrin in epidermis is of utmost importance in the treatment of dermatologic or allergic diseases or disorders. This is reported in Sandilands et al., Journal of Cell Science 122 (9), 1285-1294 or Irvine et al., The New England Journal of Medicine, 201 1 , 365 (14), 1315-1327. The present study demonstrates that a composition according to the present invention has dramatically positive effect on the filaggrin content and is therefore suitable for use as medicine, preferably for the treatment or prophylaxis of dermatologic or allergic diseases or disorders, in particular for the treatment or prophylaxis of diseases or disorders associated with filaggrin deficiencies in the epidermis.

[0056] The present composition comprising a carboxylated fructan compound, such as carboxymethylinulin, and preferably at least one salt of mono or diglycolate is able to favor the presence of water on the epidermis which is an important feature to correct wrinkles, or for lowering skin and/or mucosa ageing. Furthermore, the above data suggest that the present composition is suitable as skin or hair protective agent in a cosmetic composition, hand and/or body and/or hair care composition, sunscreen composition, or hand dishwashing detergent composition. Indeed, the testing performed in vitro demonstrate an efficient ability of the present composition to harden the epidermis and thus to avoid alteration thereof.

[0057] Example 3: In vivo testing

[0058] The efficacy and tolerance of the present composition was studied on panelists during classical clinical tests. The composition according to the present invention, used for in vivo testing, comprises 32% of carboxymethylinulin and 18% mono and diglycolate salts. Formulations comprising a defined amount of the present composition were evaluated on face, neck and forearm. Therefore, the content of carboxymethylinulin in the formulations is selected in the range defined above in the present application. The evaluation of skin moisturizing efficacy was performed with a CORNEOMETER CM825 (Courage + Khazaka). The corneometer is based on the completely different dielectric constant of water and other substances. The measuring capacitor shows changes of capacitance according to the moisture content of the samples. A glass lamina separates the metallic tracks in the probe head from skin in order to prevent current conduction in the samples. An electric scatter field penetrates the skin during the measurement and the dielectricity is determined. One track builds up a surplus of electrons the other a lack of electrons. An electric filed between the tracks with alternating attraction develops. During the measurement, the scatterfield penetrates the very first layer of the skin and determines the dielectricity. The penetration depth of the electrical scatter field is demonstrably very small, so that only the moisture on the skin is measured. Hydration of the skin was determined by evaluating the transepidermal water loss with TEWAMETER TM 300 (Courage + Khazaka). The tewameter defines the integrity of the epidermis in its normal, irritated and diseased skin. The skin smoothening efficacy was determined by SkinSys software.

[0059] Observations and the required measurements were performed over a period of three weeks with intermediate sampling. Signs and symptoms of adverse reactions, dryness, erythema, itching, burning sensation, and rashes were monitored over the duration of the study. None of the subjects experienced any adverse reaction.

[0060] The composition according to the present invention tested on panelists has unexpected efficacy in skin moisturizing, skin hydration and skin smoothening. The effect was observed irrespective of the area treated, i.e. face, neck as well forearm. An effect on skin hydration, moisturizing and smoothening was observed at least at the first week. Varying the concentration of carboxymethylinulin in the composition allow controlling the time needed to observe the effect on skin hydration, moisturizing and smoothening, thereby providing a versatile composition.

[0061] The terms and descriptions used herein are set forth by way of illustration only and are not meant as limitations. Those skilled in the art will recognize that many variations are possible within the spirit and scope of the invention as defined in the following claims, and their equivalents, in which all terms are to be understood in their broadest possible sense unless otherwise indicated. As a consequence, all modifications and alterations will occur to others upon reading and understanding the previous description of the invention. In particular, dimensions, materials, and other parameters, given in the above description may vary depending on the needs of the application.

Claims

Composition comprising:

(a) a carboxylated fructan compound and

(b) 1 to 50 wt.% of at least one salt of mono- or di-glycolate, preferably from 1 to 20 wt.%, more preferably from 1 to 10 wt.%, based on the total weight of the composition.

Composition according to claim 2 wherein said carboxylated fructan compound is selected from the group consisting of :

(a) carboxyalkylfructan having from 1 to 4 carbon atoms in the alkyl moiety,

(c) 6-carboxyfructan,

(d) fructan polycarboxylic acid, having a degree of carboxyalkylation or carboxyacylation of from 0.2 to 3.0, and

(e) mixtures thereof.

Composition according to any of the previous claims 1 or 2 wherein the carboxylated fructan compound is carboxymethylinulin having a degree of substitution of from 1.5 to 2.7.

Composition according to any of the previous claims 1 to 3 wherein said at least one salt of mono- or di-glycolate is a mixture of a mono and diglycolate salt.

Carboxylated fructan compound for use as medicine.

Carboxylated fructan compound according to claim 5 is selected from the group consisting of :

(a) carboxyalkylfructan having from 1 to 4 carbon atoms in the alkyl moiety,

(c) 6-carboxyfructan,

(e) mixtures thereof.

7. Carboxylated fructan compound according to claims 5 or 6 wherein said carboxylated fructan compound is selected from the group consisting of carboxyalkylinulin having 1 or 2 carbon atoms in the alkyl moiety and having a degree of substitution of from 1.5 to 2.7.

8. Carboxylated fructan compound according to claim 7 wherein said carboxylated fructan compound is carboxymethylinulin having a degree of substitution of from 1 .5 to 2.7.

9. Composition according to any of the previous claims 1 to 4 for use as medicine.

10. Pharmaceutical preparation comprising a therapeutically effective amount carboxylated fructan compound as defined in any of the previous claims 5 to 8 for use as medicine, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.

11. Pharmaceutical preparation according to claim 10 further comprising 1 to 100 wt.% of at least one salt of mono- or di-glycolate, preferably from 1 to 25 wt.%, more preferably from 1 to 12 wt.%, calculated on the basis of the carboxylated fructan compound.

12. Pharmaceutical preparation according to claim 1 1 wherein said at least one salt of mono- or di-glycolate is a mixture of a mono and diglycolate salt.

13. Pharmaceutical preparation according to any of the previous claims 10 to 12 wherein the content of the carboxylated fructan compound in the preparation ranges from 0.0005 wt% to 10wt% based on the total weight of the pharmaceutical preparation.

14. Carboxylated fructan compound according to any of the previous claims 5 to 8 or composition according to any of the previous claims 1 to 4 or pharmaceutical preparation according to any of the previous claims 10 to 13 for the treatment or prophylaxis of dermatologic or allergic diseases or disorders.

15. Carboxylated fructan compound or composition or pharmaceutical preparation according to claim 14 wherein said dermatologic and allergic diseases or disorders are selected from the group consisting of contact allergy, psoriasis, plaque psoriasis, psoriasis vulgaris, localized pustular psoriasis, pustule psoriasis, Hallopeau localized continuous achrodermatitis, pustular palm psoriasis, pustular sole psoriasis, generalized pustular psoriasis, von Zumbuch generalized pustular psoriasis, milia psoriasis, Hallopeau generalized continuous dermatitis, herpetiform impetigodermatitis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, numular dermatitis, generalized exfoliative dermatitis, statis dermatitis, perioral dermatitis, acne, rosacea, boils, carbuncles, pemphigus, cellulitis, Graver's disease, hidradenitis suppurativa, lichen planus, chronic lichen simplex, rhinophyma, pseudofolliculitis barbae, inflammatory reactions, drug eruptions, erythema, erythema multiforme, erythema nodosum, granuloma annulare, eczema, xerosis, ichthyosis, epidermolytic hyperkeratosis, keratoses, pruritis, cradle cap, scales, fresh stretch marks, dermatoses, burns, skin hypersensitivity reactions (including poison ivy and poison oak), decubitus ulcers, pressure ulcers, diabetic ulcers, epidermolysis bullosa, eczematoid dermatitis, pemphigus, bullous pemphigoid, epidermolysis bullosa, urticaria, angioedema, vasculitides, dermal eosinophilia, vitiligo, alopecia areata, skin cancers, cutaneous T cell lymphoma, basal cell carcinoma, nodular basal cell carcinoma, cystic basal cell carcinoma, cicatricial basal cell carcinoma, infiltrative basal cell carcinoma, Micronodular basal cell carcinoma, superficial basal cell carcinoma, pigmented basal cell carcinoma, Jacobi ulcer, fibroepithelioma of Pinkus, polypoid basal cell carcinoma, pore-like basal cell carcinoma, aberrant basal cell carcinoma, squamous cell carcinoma, adenoid squamous cell carcinoma, clear cell squamous cell carcinoma, spindle cell squamous cell carcinoma, signet-ring cell squamous cell carcinoma, basaloid squamous cell carcinoma, verrucous carcinoma, keratoacanthoma, Bowen's disease, Marjolin's ulcer, melanoma, lentigo maligna, lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, mucosal melanoma, nodular melanoma, polypoid melanoma, desmoplastic melanoma, amelanotic melanoma, soft-tissue melanoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi's sarcoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, Pagets's disease, atypical fibroxanthoma, leimyosarcoma, angiosarcoma, Merkel cell carcinoma, allergic rhinitis, hay fever and food allergy.

16. Carboxylated fructan compound or composition or pharmaceutical preparation according to claim 14 for the treatment or prophylaxis of diseases or disorders associated with filaggrin deficiencies in the epidermis.

17. Carboxylated fructan compound or composition or pharmaceutical preparation according to claim 15 or 16 wherein said diseases or disorders are selected from the group consisting of psoriasis, plaque psoriasis, psoriasis vulgaris, localized pustular psoriasis, pustule psoriasis, Hallopeau localized continuous achrodermatitis, pustular palm psoriasis, pustular sole psoriasis, generalized pustular psoriasis, von Zumbuch generalized pustular psoriasis, milia psoriasis, Hallopeau generalized continuous dermatitis, herpetiform impetigodermatitis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, numular dermatitis, generalized exfoliative dermatitis, statis dermatitis, perioral dermatitis, eczema, xerosis, ichthyosis, epidermolytic hyperkeratosis, keratoses, pruritis, eczematoid dermatitis, allergic rhinitis, contact allergy, hay fever and food allergy.

18. Use of a composition according to any of the previous claims 1 to 4, as moisture retention or absorption agent, or as epidermis hydrating agent or humectants.

19. Use of the composition according to any of the previous claims 1 to 4 as hydrating agent, humectants, or skin or hair protective agent, in a cosmetic composition, hand and/or body and/or hair care composition, sunscreen composition, or hand dishwashing detergent composition.

20. Cosmetic composition comprising a cosmetically acceptable medium and a carboxylated fructan compound as defined in any of the previous claims 5 to 8, and optionally from 1 to 100 wt.% of at least one salt of mono- or di-glycolate, preferably from 1 to 25 wt.%, more preferably from 1 to 12 wt.%, calculated on the basis of the carboxylated fructan compound.

21. Cosmetic composition according to claim 20 wherein said at least one salt of mono- or di-glycolate is a mixture of a mono and diglycolate salt.

22. Cosmetic composition according to any of the previous claims 20 or 21 wherein the content of the carboxylated fructan compound in the cosmetic composition ranges from 0.0005 wt% to 10wt% based on the total weight of the cosmetic composition.

23. Hand and/or body and/or hair care composition, sunscreen composition, or hand dishwashing detergent composition comprising a carboxylated fructan compound as defined in any of the previous claims 5 to 8, and from 1 to 100 wt.% of at least one salt of mono- or di-glycolate, preferably from 1 to 25 wt.%, more preferably from 1 to 12 wt.%, calculated on the basis of the carboxylated fructan compound.